Tissue Loss Research Articles

Mid-Term Results of Popliteal-Pedal Inframalleolar Vein Bypasses in Chronic Limb-Threatening Ischemia Patients After Previous Failed Tibial Endovascular Recanalization

Inframalleolar bypass still preserves its role in the modern endovascular era. Aim of this study was to evaluate the mid-term outcomes of "short" inframalleolar vein bypasses in patients with chronic limb-threatening ischemia (CLTI) after previous failed tibial endovascular recanalization. Between January 2015 and December 2021 107 CLTI patients in 3 Italian Departments of Vascular Surgery underwent "short" inframalleolar vein bypass after failed tibial endovascular recanalization. Early (30-day) and 3-year outcomes were evaluated in terms of survival, primary patency, primary assisted patency, secondary patency, and amputation-free survival. Univariate analysis of the perioperative factors affecting outcomes were performed by means of log-rank test. Associations of procedure variables were sought based on a multivariate Cox regression analysis. Distal anastomosis (inframalleolar) was mostly performed on dorsal pedis (64, 59.8%). At 30 days bypass occlusion was recorded in 5 cases (4.6%). Mean follow-up period was 20.5 ± 17.9 months. Estimated 3-year overall survival was 66.7%. Three-year estimates of primary patency, primary assisted patency, secondary patency, and amputation-free survival were 68.5%, 70.1%, 70.2%, and 76.7%, respectively. Multivariate analysis showed a negative association of insulin treatment with primary patency (HR 4.3, p = .04), primary assisted patency (HR 5.1, p = .02), and secondary patency (HR 5.1, p = .02). Negative association of long-term corticosteroid use was also found with primary patency (HR 7.8, p = .005), primary assisted patency (HR 8.7, p = .003), secondary patency (HR 8.7, p = .003), and amputation-free survival (HR 3.9, p = .05). "Short" vein bypasses to the foot arteries in CLTI patients yielded good mid-term overall patency, and limb salvage rates after a failed tibial endovascular recanalization. Insulin dependent diabetes mellitus, and long-term corticosteroid use seemed to affect the outcomes.

Incidence of Angiographic Deterioration Following Inframalleolar Angioplasty and Its Impact on Outcomes in Patients With Chronic Limb-Threatening Ischemia Requiring Repeat Intervention

Incidence of Angiographic Deterioration Following Inframalleolar Angioplasty and Its Impact on Outcomes in Patients With Chronic Limb-Threatening Ischemia Requiring Repeat Intervention

The Comorbidity-Polypharmacy Score as a Predictive Tool of Survival and Limb Salvage in Patients Undergoing Lower Limb Revascularization Procedures for Chronic Limb-Threatening Ischemia

ObjectiveThe comorbidity-polypharmacy score (CPPS) was created to evaluate the clinical burden of comorbidities in geriatric patients. It represents an objective tool to stratify patients’ risk in different settings. The study aimed to evaluate CPPS in predicting mortality and amputation in patients undergoing elective revascularization procedures in CLTI patients. MethodsThis is 2 years retrospective single-centre study. We included all patients undergoing elective lower-limb revascularization procedures admitted with CLTI diagnosis. Four CPPS groups were defined: mild, moderate, severe and morbid. The primary early and long-term outcomes were 30-day overall mortality, 30-day amputation rate and overall survival and limb salvage respectively. ResultsA total of 442 patients were enrolled in the study. Mean age was 76.5±9.9 years and 61.5% (272/442) were male. CPPS was calculated: 22.6% (100/442) have mild CPPS, 54.3% (240/442) moderate, 21.9% (97/442) severe and 1.2% (5/442) morbid.Kaplan-Meier curves for overall survival stratified for CPPS grade highlighted a strong statistically significant difference (p<0.0001) among the four CPPS classes.Mild CPPS has significantly higher limb salvage rate among moderate, severe and morbid CPPS groups (p<0.0001). Limb salvage for mild and severe CPPS, at 36 months was 95% vs. 85.1% respectively.Stepwise multivariable Cox-analysis revealed that mortality was independently associated with dialysis, Rutherford Classification V, age and CPPS. Male sex, multilevel arterial disease, and hybrid surgical repair were independently associated with amputations. ConclusionCPPS is a straightforward tool to evaluate the patient’s complexity and could be used as an adjuvant tool to stratify early- and long-term outcomes in CLTI patients undergoing elective revascularization procedures.

Perceptions, Barriers and Facilitators Regarding Nutritional Care for Patients with Chronic Limb Threatening Ischemia: A Focus Group Study Among Healthcare Professionals

Nutrition and nutritional care are essential for optimal outcomes, and, therefore of importance for patients with chronic limb threatening ischemia (CLTI) given their high risk of complications. However, insight is lacking in how healthcare professionals directly involved in the care of patients with CLTI perceive nutritional care, as well as in the perceived barriers and facilitators regarding optimal nutritional care. In this qualitative study with a phenomenological approach, three online focus groups were conducted with various healthcare professionals directly involved in the care of patients with CLTI. Sample size was guided by information power. Focus group recordings were transcribed verbatim, and reflexive thematic analysis was performed. Seventeen healthcare professionals participated, including vascular surgeons, fellows in vascular surgery, a medical doctor and researcher, nurse specialized in wound care, general nurse, physical therapists, dietitians, and nutrition assistants. Four themes were generated: (1) nutritional care is crucial for optimal clinical outcomes and a healthy life, (2) insufficient attention to undernutrition and nutritional care by healthcare professionals, (3) patient-related factors challenge healthcare professionals in providing nutritional care, and (4) need for optimizing the organizational process related to nutritional care. Perceived barriers regarding nutritional care included knowledge deficits, nutritional care not being part of the healthcare professionals' routine, missing tools to identify undernutrition, patient-related factors, and time constraints. Facilitators regarding nutritional care included more scientific evidence regarding the effect of nutritional care on clinical outcomes and optimization of organizational processes related to nutritional care. Healthcare professionals perceive nutritional care as important for optimal outcomes, but nutritional care is not routinely implemented in the care of patients with CLTI. This lack of implementation of nutritional care may be due to the barriers perceived in various domains. The findings of this study stress the need to optimize nutritional care, with the aim of improving outcomes in the CLTI population.

Predictive Ability of the Pedal Medial Arterial Calcification Score for Major Adverse Limb Events Among Patients with Chronic Limb-Threatening Ischemia

ObjectivePedal medial arterial calcification (pMAC) is a potential predictor of major adverse limb events (MALE) among patients with critical limb-threatening ischemia (CLTI). This study aims to validate the prognostic value of the pMAC score in predicting major lower limb amputation (MLLA) and need for re-do revascularisation. MethodsA single centre study involving 196 patients diagnosed with CLTI, reviewed between 2012 and 2022. Patients’ pMAC scores were obtained through X-ray assessments. Correlations between pMAC scores and the incidence of MALE and re-do revascularisation, were analysed. A power analysis using G* Power 3 software determined a needed sample size of 157 participants. Statistical analysis employed SPSS 26, utilising descriptive statistics, Chi Square, Mann-Whitney, Kaplan-Meier with log-rank test, and Cox regression for predictor identification. ResultsThe cohort was predominantly male (79.1%) and diabetic (59.2%). Re-do revascularisation need was 15.3%, increasing with pMAC scores: 3.3% (low), 24.5% (medium), and 50% (high) (p<0.001). MLLA frequency also rose with pMAC scores: 6.7%, 27.5%, and 50% respectively (p<0.001). Higher pMAC scores correlated with a higher incidence of MALE (p=0.029). Multivariate analysis showed medium pMAC (HR 4.159, p=0.002), high pMAC (HR 7.366, p=0.015), and GLASS stage 3 (HR 3.529, p=0.011) as independent MLLA predictors. Re-do revascularisation predictors included female sex (HR 2.106, p=0.063), Black race (HR 64.498, p=0.001), medium pMAC (HR 6.812, p=0.002), high pMAC (HR 11.455, p=0.008), and GLASS stage 3 (HR 2.899, p=0.037). ConclusionThe pMAC score effectively predicts MALE in CLTI patients and enhances risk stratification. Using both, pMAC scores and GLASS stages enhances predictive accuracy, identifying patients at higher risk for MLLA, Informing clinical decision-making and therapeutic strategies.

The Role of Intravascular Ultrasound in Limb Salvage: A Systematic Review and Meta-Analysis.

The purpose of this study was to review the current literature of intravascular ultrasound (IVUS) use in real world cohorts inclusive of chronic limb threatening ischemia (CLTI) patients and compare the outcomes to patients imaged by angiography alone. The systematic review was registered in Research Registry. A literature search was performed across 4 databases: PubMed, Medline/Embase, Cochrane Review, and Web of Science for eligible comparative studies. The primary outcomes examined were clinically driven target lesion revascularization (CD-TLR), amputation (including minor below the ankle and major above the ankle), all-cause mortality, limb salvage and mean balloon dilation. A random effects model was used when pooling outcomes to account for heterogeneity. Publication bias was determined using eggers test and illustrated on a funnel plot. Six studies were included in this review, with a total of 1883 subjects with Rutherford 1-6. Among the 1883 subjects, 940 had Rutherford 4-6. IVUS was used in 1294 subjects and angiography alone was used in 589 subjects. Pooled analysis determined no significant association in IVUS + angiography with CD-TLR (O.R = 1.43 [CI: 0.80, 2.58]), all-cause amputation (O.R = 0.63 [CI: 0.34, 1.17]), and all-cause mortality (O.R = 0.63 [CI: 0.34, 1.17]). Sub analysis of subjects with CLTI, Rutherford classes 4-6 showed an association between IVUS + angiography use with limb salvage at 1 year, O.R = 2.22 [1.24, 3.97]. The use of IVUS + angiography compared to angiography alone showed larger reference vessel diameter in both all-inclusive Rutherford classifications and the CLTI subset. The use of IVUS + angiography compared to angiography alone showed no difference in CD-TLR at 12 months, lower extremity amputation, and all-cause mortality for Rutherford 1-6. The use of IVUS + angiography compared to angiography alone in the CLTI subset analysis improved limb salvage.

Outcomes among Patients with End-Stage Kidney Disease and Chronic Limb-Threatening Ischemia: A Population-based Cohort Study.

To understand mortality and secondary outcomes in patients with both end-stage kidney disease (ESKD) and chronic limb-threatening ischemia (CLTI) after no procedural treatment, primary amputation, endovascular treatment, and open surgery. ESKD and CLTI commonly cooccur and limited prior work has demonstrated poor outcomes including one-year survival despite treatment. We conducted a retrospective national cohort study of United States Renal Data System data from January 1, 2016 to December 31, 2019 to determine mortality, major postoperative complications, and other outcomes. We performed an exploratory analysis comparing two-year survival by treatment using propensity matching. Of 1,876,652 records with a CLTI diagnosis, we identified 3,908 patients with ESKD and an incident CLTI diagnosis. Mean age at CLTI diagnosis was 65.7 years and 2,405 (61.5%) were male. 2,696 (69.0%) had no procedural treatment, 609 (15.6%) had major limb amputation, 439 (11.2%) had endovascular treatment, and 164 (4.2%) had open surgery. There was 44.9% mortality at one year, along with 41.8% major postoperative complications and 52.6% readmissions at 90 days. Comparing two-year survival, we found no differences between the amputation and endovascular cohorts (P=0.08) and between endovascular and open (P=.06). There was superior two-year survival in the open surgery cohort compared to the amputation cohort (P=0.002). Patients living with both ESKD and CLTI experience poor outcomes irrespective of treatment. Exploratory analyses demonstrated that two-year survival among the three principal procedural treatments was similar except for superior survival among patients undergoing open therapy compared to primary amputation.

Great Saphenous Vein Arterialization in Patients with Severe Chronic Limb Threatening Ischemia: A Last Resort for Limb Salvage

ObjectiveIn one-fifth of patients with chronic limb-threatening ischemia there are no revascularisation options. In those cases, venous arterialisation could be a last resort for limb salvage. This study examines the clinical outcome of 17 patients, with non-healing wounds (Fontaine 4), who underwent Great Saphenous Vein (GSV) arterialisation leaving the distal saphenous side branches open and avoiding incisions in the lower leg and foot. MethodsIn this retrospective study all the patients who underwent GSV arterialisation between 1 January 2020 and 1 October 2023 were included. During the procedure, a small incision was made in the groin to identify the GSV and SFA. The GSV was detached from the deep venous system, the upper leg side branches were ligated, and the side branches distal to the knee joint were left open to create a pressure drop. Valvulotomy of the GSV down to the foot was performed in all patients. This approach does not necessitate the use of grafts or stents so that a serious infected foot can also be treated. For this study we have analysed the Limb salvage, wound healing, and mobility after treatment and observed pre and postoperative skin oxygenation over a one-year period. ResultsThis intervention resulted in a limb salvage rate of 46% and a secondary patency of 88% after one year in cases where amputation would have otherwise been necessary. Pre- and postoperative TcPO2 measurements indicated a gradual but consistent increase in skin oxygenation in 71% of the patients with a GSV larger than 3mm, underscoring the importance of future patient selection. All patients who successfully received arterialisation showed complete wound healing and improved mobility. ConclusionThis study introduced a promising approach to venous arterialisation in patients with severe CLTI who have no other treatment options, potentially impacting disease burden and quality of life significantly.

PROBLEMS OF CHOOSING A METHOD OF DENTAL TREATMENT OF TEETH AFTER ENDODONTIC INTERVENTION

The optimal way to restore the anatomical structure of teeth after endodontic intervention is a controversial topic. Teeth after endodontic intervention have different properties compared to intact living teeth. Changes in these properties are associated with volumetric loss of hard tissues, caries, final preparation of the cavity taking into account access to endodontic treatment. Choosing the optimal method of dental treatment of teeth requires compliance with many factors, such as: prevention of infection penetration into root canals, restoration of tooth contacts, restoration of chewing functions, protection against further carious and non-carious destruction, restoration of tooth aesthetics. Dentists are now more than ever aware of the interdependence of the endodontic and restorative aspects of dental treatment and how much this will affect achieving the best long-term outcome. Controversies of the clinical relevance of endodontic and restorative treatment choice issues are mostly unanswered based on clinical data and scientific evidence. The modern approach to tooth restoration after endodontic intervention is an important topic. To improve clinical outcomes, it is important to determine the effectiveness of treatment, the importance of preserving tooth structure, the choice of treatment method with restorative materials, and the integration of digital dentistry to improve diagnosis and treatment principles. Research rationale. The purpose of this study is to find and use literature data on the effectiveness of modern methods of dental treatment after endodontic intervention in Ukraine. Materials and methods. Scientific data from a review and systematic analysis of the literature were used. Materials were searched using the Google Scholar, PubMed, Google Scholar databases and open sources of the World Health Organization, the Ministry of Health of Ukraine and other government web portals of Ukraine. Results, Discussion. After conducting a literature analysis to compare the effectiveness of using cast metal inserts and fiberglass posts, we can come to the conclusions that retrospective studies on the relationship between successful restorations and such factors as the type of tooth, the volume of residual hard tissues, the number of occlusal contacts, the type of the final restoration and the position of the tooth in the dental arch are the main criteria for choosing a treatment method. A controversial choice is that metal abutments are associated with a higher risk of root fracture, their manufacture requires laboratory techniques, while the use of fiberglass posts is associated with a higher risk of decementation, and overloading of fiberglass posts leads to their fractures. Conclusions. Decision-making and the choice of methods of dental treatment after endodontic intervention remain difficult. However, the interdependence of endodontic treatment and restoration of the crown part of the tooth is clearly established. Physicians must consider both aspects of treatment equally to ensure the best possible outcomes for their patients. The use of digital scanning enables an accurate volumetric assessment of the residual hard tissues of the tooth, which can be used to provide tangible qualitative results of the analysis and decision-making with the choice of treatment method. The choice of treatment method is not defined in a single protocol and requires further careful study with new experimental developments, based on the latest technologies of world leaders in dentistry.

Preliminary application of ulnar cortex transverse transport technique in treatment of upper extremity thromboangiitis obliterans

To investigate the feasibility and effectiveness of ulnar cortex transverse transport technique in treating upper extremity thromboangiitis obliterans (TAO). A retrospective analysis was conducted on the clinical data of 7 male patients with upper extremity TAO who were admitted and met the inclusion criteria between January 2019 and July 2022. The patients ranged in age from 32 to 50 years, with a mean age of 40.1 years. The disease duration ranged from 6 to 24 months, averaging 13.6 months. The smoking history ranged from 8 to 31 years, with a mean of 18.4 years. All patients presented with finger ulcers or gangrene, including 1 case affecting the thumb and index finger, 1 case affecting the index and middle fingers, 1 case affecting the middle and ring fingers, 1 case affecting only the ring finger, and 3 cases affecting the ring and little fingers. The preoperative visual analogue scale (VAS) score was 9.1±0.7. All patients underwent treatment with the ulnar cortext transverse transport technique. The wound healing time and the disappearance time of rest pain were recorded. The VAS score was used to assess the degree of hand pain before and after operation. Serum interleukin 6 (IL-6) levels were measured before operation and at 1 month after operation. Computed tomography angiography (CTA) of the affected limb was performed before operation and at 3 months after operation to evaluate changes in blood vessels. The clinical outcomes were evaluated at 1 year after operation based on the Patwa and Krishnan grading system. All 7 patients were followed up 12-17 months, with an average of 13.7 months. All patients experienced successful healing of ulcers, with wound healing time ranging from 14 to 21 days, averaging 17.3 days. During the follow-up, no complication occurred, and there was no recurrence of ulcers. The disappearance time of rest pain ranged from 8 to 15 days, averaging 12.1 days. The pre- and post-operative (1-month) serum IL-6 levels were (25.1±5.9) pg/mL and (11.9±2.9) pg/mL, respectively, with a significant difference ( t=5.363, P=0.002). CTA examination at 3 months after operation revealed partial revascularization of upper extremity arteries and establishment of collateral circulation, showing significant improvement compared to preoperative status. The VAS scores at 1, 7, 28 days, and 6 months postoperatively were 6.4±0.8, 3.7±0.8, 0.6±0.8, and 0.1±0.4, respectively, all of which significantly improved compared to preoperative scores ( P<0.05). Furthermore, the VAS scores gradually decreased over time, with significant differences observed between postoperative time points ( P<0.05). At 1 year after operation, the effectiveness of all 7 patients were evaluated as excellent based on the Patwa and Krishnan grading system. The ulnar cortex transverse transport technique can improve blood circulation in the upper limb of patients with TAO, reconstruct microcirculation, inhibit inflammation, promote ulcer healing, and alleviate limb pain.

Successful Pedal Bypass in a Patient With Pseudoxanthoma Elasticum.

Pseudoxanthoma elasticum (PXE) is a rare metabolic disease, causing calcification in the arterial media layer and further peripheral artery disease (PAD). A high rate of failure has been reported after endovascular and open surgical management of PAD among patients with PXE. Critical limb ischemia (CLI) rarely develops in PXE, and there are only few reports of its treatment. We present a case report of a 57year-old female diagnosed with pseudoxanthoma elasticum (PXE). She presented with critical limb ischemia (CLI) and was successfully treated with pedal bypass using the great saphenous vein. Despite obtaining suboptimal outcomes through the initial approach of percutaneous transluminal angioplasty to treat critical limb ischemia, the subsequent bypass operation proved to be a success. At the first follow-up appointment at 1month, the patient was asymptomatic and the ulceration had almost healed. The patient underwent an ultrasound examination at 3, 6, 12, and 24months after discharge, and the surveillance was uncomplicated. With a clear indication for surgery, limb-threatening ischemia can be successfully treated with distal bypass, if necessary, in patients with PXE similarly to atherosclerotic PADs. Appropriate diagnostic and surveillance imaging and the utilization of a multidisciplinary team are key components for effective management of PAD in patients with PXE.

Results of innervated digital artery perforator flap and direct-flow homodigital flap application in fingertip soft tissue amputations

ObjectiveThe purpose of this study is to compare the results of the innervated digital artery perforator (IDAP) flap and the direct-flow homodigital flap as reconstruction methods for fingertip soft tissue amputations. This issue is important in hand surgery, and we aim to identify the method that provides the best functional and cosmetic outcomes.MethodsBetween 2020 and 2022, 32 patients with fingertip amputations were reconstructed by the same surgeon using two different methods. The patients were retrospectively divided into two groups: those who underwent IDAP (n = 14) and those who had a direct-flow homodigital flap (n = 18). We compared the groups in terms of defect size, cold intolerance, venous congestion, Sollerman hand function test scores, Seddon sensory test scores, and follow-up periods, as well as flap viability, flexion contracture, and static two-point discrimination (s2PD).ResultsOf the 32 patients (26 men, 6 females; age: mean 28.72 ± 11.5 years), the injuries were caused by different mechanisms, including sharp (57.1% IDAP), crush (75% IDAP) and entanglement (66.7% homodigital). The average area of tissue loss was approximately 2.70 ± 1.37 cm², while the average s2PD measurement was approximately 4.94 ± 1.04 mm. Postoperatively, the Seddon sensory test results for the homodigital flap group were S4 (61.5%), S3 (23.1%), S3+ (7.7%), and S2 (7.7%), compared to the IDAP group, which showed S4 (57.9%), S3+ (21.1%), and S3 (21.1%). Complications occurred in five patients, though no flap loss or revision was required. The postoperative mean Sollerman hand function scores were higher for the homodigital group than for the IDAP group, with values of 75 ± 2.64 and 73 ± 3.34, respectively. Although not statistically significant, the results numerically suggest that the IDAP flap is better in terms of sensory recovery and hand function compared to the homodigital flap (p > 0.05).ConclusionsThis is the first investigation to compare direct-flow flaps with IDAP. The average follow-up period for patients who underwent homodigital surgery was also shorter than that of the IDAP group. Furthermore, the mean postoperative two-point discrimination and postoperative Sollerman function score were higher in patients who had homodigital surgery.

Interobserver and inter-modality concordance of quiescent interval slice selective magnetic resonance angiography and CT angiography in assessment of critical lower limb ischemia

BackgroundWe evaluated the noncontrast MRA as an alternate method to CT angiography in assessment of patients with lower limb ischemia, 30 patients were included in a prospective cohort study; they underwent quiescent interval slice selective magnetic resonance angiography (QISS-MRA) and computed tomographic angiography (CTA). The assessment of images was evaluated by two independent consultants. The overall subjective image quality, interobserver and intermodality concordance were calculated.ResultsThe median acquisition time in QISS-MRA was 20 min (range 18–30 min), The overall subjective image quality was rated similarly with QISS-MRA (3.13 [95% CI 2.84–3.42]) and CTA (3.23 [95% CI 2.94–3.52]; p = 0.08) with interobserver concordance for lesion ratings in QISS-MRA reached (κ = 0.987 (SD 0.006)), while for CTA it was (κ = 0.99 (SD 0.006)), while the intermodality concordance between QISS-MRA and CTA in lesion ratings were calculated on a per segment basis and was (κ = 0.944 (SD 0.013)) for reader 1 and (κ = 0.947 (SD 0.013)) for reader 2, with sensitivity 100% and specificity 97.6%ConclusionsQISS-MRA is a reliable modality for assessment of patients with critical limb ischemia.

Selective neuronal expression of progranulin is sufficient to provide neuroprotective and anti-inflammatory effects after traumatic brain injury

Progranulin (PGRN), which is produced in neurons and microglia, is a neurotrophic and anti-inflammatory glycoprotein. Human loss-of-function mutations cause frontotemporal dementia, and PGRN knockout (KO) mice are a model for dementia. In addition, PGRN KO mice exhibit severe phenotypes in models of traumatic or ischemic central nervous system (CNS) disorders, including traumatic brain injury (TBI). It is unknown whether restoration of progranulin expression in neurons (and not in microglia) might be sufficient to prevent excessive TBI-evoked brain damage. To address this question, we generated mice with Nestin-Cre-driven murine PGRN expression in a PGRN KO line (PGRN-KONestinGrn) to rescue PGRN in neurons. PGRN expression analysis in primary CNS cell cultures from naïve mice and in (non-) injured brain tissue from PGRN-KONestinGrn revealed expression of PGRN in neurons but not in microglia. After experimental TBI, examination of the structural brain damage at 5 days post-injury (dpi) showed that the TBI-induced loss of brain tissue and hippocampal neurons was exacerbated in PGRN-KOGrnflfl mice (PGRN knockout with the mGrn fl-STOP-fl allele, Cre-negative), as expected, whereas the tissue damage in PGRN-KONestinGrn mice was similar to that in PGRN-WT mice. Analysis of CD68+ immunofluorescent microglia and Cd68 mRNA expression showed that excessive microglial activation was rescued in PGRN-KONestinGrn mice, and the correlation of brain injury with Cd68 expression suggested that Cd68 was a surrogate marker for excessive brain injury caused by PGRN deficiency. The results show that restoring neuronal PGRN expression was sufficient to rescue the exacerbated neuropathology of TBI caused by PGRN deficiency, even in the absence of microglial PGRN. Hence, endogenous microglial PGRN expression was not essential for the neuroprotective or anti-inflammatory effects of PGRN after TBI in this study.Graphical

Assessment of nutrient amendments on stony coral tissue loss disease in Southeast Florida

Assessment of nutrient amendments on stony coral tissue loss disease in Southeast Florida

Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia - a narrative review.

Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or "no-option" CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of "no-option" Atherosclerotic Peripheral Arterial disease / Buerger's disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.

Percutaneous Deep Venous Arterialization by Balloon Angioplasty without Stent Implantation for Patients with Chronic Limb-Threatening Ischemia Undergoing Hemodialysis: A Retrospective Cohort, Single-Center, Single-Arm Study.

This retrospective, single-center study aimed to determine the efficacy of percutaneous deep venous arterialization in patients on hemodialysis with chronic limb-threatening ischemia. Twenty-one consecutive limbs on hemodialysis with chronic limb-threatening ischemia were treated with percutaneous deep venous arterialization using balloon angioplasty following a failed pedal arterial reconstruction between May 2021 and June 2022. An arteriovenous fistula near the ankle joint was created to ensure sufficient venous flow reversal to the pedal veins. In case of occlusion of the tibial artery, a guidewire was advanced (subintimal) to the ankle joint vicinity was technically important. The primary outcome measures were the 6-month complete wound healing and freedom from major amputation rates; the secondary outcome measure was the 6-month amputation-free survival. Occlusion of all pedal arteries was observed in 17 limbs (81.0%). Arteriovenous fistulas were predominantly created at the distal portions of the posterior tibial artery and vein in 18 limbs (85.7%). No extravasation at the fistulas was observed. Re-intervention was required in 16 limbs (76.2%) due to tibial artery or deep vein occlusion. The 6-month complete wound healing rate was 42.9% (nine limbs), with a median healing time of 85 days (interquartile range: 58-151 days). The 6-month freedom from major amputation and amputation-free survival rates were 90.5% (19 limbs) and 61.9% (13 limbs), respectively. Balloon angioplasty without stent implantation for percutaneous deep venous arterialization is promising for improving the complete wound healing and amputation-free survival rates after pedal artery reconstruction failure. Level 3b, retrospective cohort study.

Type 3c diabetes mellitus: what are we dealing with? Review

The authors presented updated data on the term «type 3 diabetes mellitus», its modern classification, pathophysiological mechanisms of development and features of treatment, its definitions, epidemiology and modern classification based on the recommendations of the American Diabetes Association. Definitions and epidemiological features of acute pancreatitis and its most frequent complications, including 3c type diabetes have been described. Statistical data were presented on the risk of developing complications of acute pancreatitis in the form of carbohydrate metabolism disorders. Historical prerequisites of fatal complications of acute pancreatitis in the form of hyperglycemic states were also described. The pathophysiological mechanisms of the development of type 3c diabetes, namely local and systemic inflammation, loss of islet tissue of the pancreas, dysregulation of the insulin­­incretin axis, autoimmune destruction of β­cells of the pancreas, etc. were highlighted in detail. The role of genetic factors in the development of diabetes against the background of acute pancreatitis is described. Currently there are no standardized unified criteria of type 3c diabetes, thus the main and additional diagnostic criteria according to the different authors have been analyzed in detail. The differential characteristics and features of the diagnosis of diabetes mellitus by type and peculiarities of the diagnosis of type 1, 2 and 3c diabetes mellitus have been presented. The discussion on the glycemic target goals for patients with type 3c diabetes and the need for screening and prevention of carbohydrate metabolism disorders in patients with acute pancreatitis has been outlined. The authors provided current recommendations for the treatment of type 3c diabetes and discussed the possibilities of the use of insulin in the basis/bolus mode to achieve compensation of carbohydrate metabolism. The necessity to compensate pancreas exocrine insufficiency to improve the assimilation of fats and fat‑soluble vitamins has been emphasized.

Minimally invasive caries treatment

The development of minimally invasive caries treatment has dramatically changed dentistry. Instead of traditional, often invasive methods that resulted in significant loss of healthy dental tissue, this approach focuses on preserving the vitality of the pulp and minimizing tissue loss by delaying and scaling back restorative treatments. This involves the use of modern methods, with selective caries removal with or without indirect (pulp) capping being the norm for treating extensive lesions. The philosophy of minimal intervention goes beyond treatment choices to include a holistic approach from diagnosis to follow-up care, emphasizing personalized care based on risk profiles. This paradigm shift has greatly improved the standard of care, but continued attention to the risks of overdiagnosis and overtreatment is necessary to ensure optimal oral health.

Dietary lipid is largely deposited in skin and rapidly affects insulating properties.

Skin has been shown to be a regulatory hub for energy expenditure and metabolism: mutations of skin lipid metabolism enzymes can change the rate of thermogenesis and susceptibility to diet-induced obesity. However, little is known about the physiological basis for this function. Here we show that the thermal properties of skin are highly reactive to diet: within three days, a high fat diet reduces heat transfer through skin. In contrast, a dietary manipulation that prevents obesity accelerates energy loss through skins. We found that skin was the largest target in a mouse body for dietary fat delivery, and that dietary triglyceride was assimilated both by epidermis and by dermal white adipose tissue. Skin from mice calorie-restricted for 3 weeks did not take up circulating lipids and showed a highly depleted stratum corneum. Dietary triglyceride acyl groups persist in skin for weeks after feeding. Using multi-modal lipid profiling, we have implicated both keratinocytes and sebocytes in the altered lipids which correlate with thermal function. In response to high fat feeding, wax diesters and ceramides accumulate, and triglycerides become more saturated. In contrast, in response to the dramatic loss of adipose tissue that accompanies restriction of the branched chain amino acid isoleucine, skin becomes more heat-permeable, resisting changes induced by Western diet feeding, with a signature of depleted signaling lipids. We propose that skin should be routinely included in physiological studies of lipid metabolism, given the size of the skin lipid reservoir and its adaptable functionality.